The E3 Ubiquitin Ligase SYVN1 Ubiquitinates Atlastins to Remodel the Endoplasmic Reticulum Network

Yupeng Zhao; Zhigang Feng; Yan Zou; Yanfen Liu

doi:10.1016/j.isci.2020.101494

The E3 Ubiquitin Ligase SYVN1 Ubiquitinates Atlastins to Remodel the Endoplasmic Reticulum Network

iScience. 2020 Aug 24;23(9):101494. doi: 10.1016/j.isci.2020.101494. eCollection 2020 Sep 25.

Authors

Yupeng Zhao^{1

2

3}, Zhigang Feng^{1

4

3}, Yan Zou^{1

4

3}, Yanfen Liu^{1

2

3}

Affiliations

¹ School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
² CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
³ University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.

Abstract

Atlastin (ATL) is a class of dynamin-like GTPases shaping endoplasmic reticulum (ER) by mediating homotypic membrane fusion. Defect of ATLs leads to abnormal ER structure and hereditary spastic paraplegia (HSP), a neurodegenerative disease with progressive spasticity. How ATLs are regulated to maintain the ER dynamics is not clear. Here, we found that SYVN1, an E3 ubiquitin ligase on the ER membrane, regulates ER shape and COPII exporting by mediating ubiquitination on ATLs, especially ATL1. ATL1 is ubiquitinated by SYVN1 strongly on K285 and mildly on K287. Ubiquitination on ATL1 does not result in protein degradation but inhibits ATL1 GTPase activity. SYVN1 overexpression compensates the excessive ER network fusion caused by ATL1 overexpression. Accordingly, the role of SYVN1 and ATL1 in regulating ER morphology is also recapitulated in Caenorhabditis elegans. Taken together, our study reveals a different role of SYVN1 in ER remodeling through mediating ubiquitination on ATLs.

Keywords: Biological Sciences; Cell Biology; Molecular Biology.